Probing Miscibility of Spray-Dried and Melt-Quenched Amorphous Dispersions Using Rheology and Solid-State NMR Spectroscopy

A c*-guided high-temperature rheological approach and solid-state NMR (ssNMR) ¹H T1ρ and ¹H T₁ relaxation time measurements were used to estimate the miscibility of celecoxib (CEL)/polyvinylpyrrolidone (PVP) amorphous solid dispersions (ASDs) prepared by melt quench and spray drying. The ssNMR spin diffusion method is capable of investigating the miscibility of ASDs processed by the two methods, as it measures as-is ASD powders, while the c*-guided high-temperature rheological approach cannot, since it erases the processing history. Our results indicate a general agreement of the estimated miscibility of ASDs prepared by the two processing methods. The crystallization tendency is significantly different when the polymer concentration c is below and above c*. When c < c*, the onset of crystallization in dilute CEL/PVP ASDs is approximately identical to that of neat amorphous CEL. However, when c > c*, the first evidence of CEL crystallization is significantly delayed, indicating a reduced crystallization propensity. These results confirm that the efficient and material-sparing rheological approach can be used to estimate the miscibility (limit) and predict stability against crystallization for both melt-extruded and spray-dried ASDs. Our findings are useful in the rational and efficient design of robust ASDs with a desirable stability against crystallization during long-term storage.